Tachyplesin I (TPI) is a cationic β-hairpin antimicrobial peptide with broad-spectrum, potent antimicrobial activity. In this study, the all d-amino acid analogue of TPI (TPAD) was synthesized, and its structure and activity were determined. TPAD has comparable antibacterial activity to TPI on 14 bacterial strains, including four drug-resistant bacteria. Importantly, TPAD has significantly improved stability against enzymatic degradation and decreased hemolytic activity compared to TPI, indicating that it has better therapeutic potential. The induction of bacterial resistance using low concentrations of TPAD resulted in the activation of the QseC/B two-component system. Deletion of this system resulted in at least five-fold improvement of TPAD activity, and the combined use of TPAD with LED209, a QseC/B inhibitor, significantly enhanced the bactericidal effect against three classes of multidrug-resistant bacteria.Recently, our group identified that harmine is able to induce β-cell proliferation both in vitro and in vivo, mediated via the DYRK1A-NFAT pathway. Since, harmine suffers from a lack of selectivity, both against other kinases and CNS off-targets, we therefore sought to expand structure-activity relationships for harmine's DYRK1A activity, to enhance selectivity for off-targets while retaining human β-cell proliferation activity. We carried out optimization of the 9-N-position of harmine to synthesize 29 harmine-based analogs. Several novel inhibitors showed excellent DYRK1A inhibition and human β-cell proliferation capability. An optimized DYRK1A inhibitor, 2-2c, was identified as a novel, efficacious in vivo lead candidate. https://www.selleckchem.com/products/ABT-263.html 2-2c also demonstrates improved selectivity for kinases and CNS off-targets, as well as in vivo efficacy for β-cell proliferation and regeneration at lower doses than harmine. Collectively, these findings demonstrate that 2-2c is a much improved in vivo lead candidate as compared to harmine for the treatment of diabetes.A three-dimensional graphene (GE) segregated network structure is of significance for improving the conductivity of composites. However, constructing such a GE network structure in composites still remains a challenge. Here, we demonstrate a facile process, that is, liquid-phase redispersion and self-assembly (LRS) to prepare polymer nanocomposites with graphene segregated networks. High shear liquid-phase mixing accompanied by the diffusion of dissolved polymer chains into the interstices and voids of the loose graphene powders can lead to redispersion of GE in polymer solution. Once the stirring is stopped, the self-assembly and segregation of redispersed GE occurs in a poor solvent driven by π-π interaction. After solvent evaporation, the GE assembly structures are retained as networks in the GE/polymer composite prepared by hot pressing. The graphene/(isobutylene-isoprene rubber) nanocomposite (GE/IIR) was investigated as a demonstration for the advantages of the LSR method. The morphologies of GE assemblies in the liquid phase and GE networks in the solid composite were observed. Due to the existence of the homogeneously distributed graphene segregated networks, the tensile strength and elongation at break for GE/IIR nanocomposites increase by ?410 and ?126%, respectively, and the electrical conductivity reaches ?100 S m-1 at a GE content of 3.76 vol %. The LRS method was also successfully tried for systems with different polymer matrixes and different solvents, suggesting the robustness of the proposed method. The prepared flexible GE/IIR nanocomposites with GE networks are sensitive to tiny strain and can be applied in wearable sensors for the detection of human physiological signals.A two-dimensional topological insulator features (only) one bulk gap with nontrivial topology, which protects one-dimensional boundary states at the Fermi level. We find a quantum phase of matter beyond this category a multiple topological insulator. It possesses a ladder of topological gaps; each gap protects a robust edge state. We prove a monolayer of van der Waals material PtBi2 as a two-dimensional multiple topological insulator. By means of scanning tunneling spectroscopy, we directly visualize the one-dimensional hot electron (and hole) channels with nanometer size on the samples. Furthermore, we confirm the topological protection of these channels by directly demonstrating their robustness to variations of crystal orientation, edge geometry, and sample temperature. The discovered topological hot electron materials may be applied as efficient photocatalysts in the future.This work aims to utilize diamond-like carbon (DLC) thin films for bioreceptor immobilization and amperometric biosensing in a microfluidic platform. A specific RF-PECVD method was employed to prepare DLC thin film electrodes with desirable surface and bulk properties. The films possessed a relatively high sp2 fraction, a moderate electrical conductivity (7.75 × 10-3 S cm-1), and an optical band gap of 1.67 eV. X-ray photoelectron spectroscopy (XPS) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy revealed a presence of oxygen-containing functional groups on the DLC surface. The DLC electrodes were integrated into polydimethylsiloxane (PDMS) microfluidic electrochemical cells with the channel volume of 2.24 μL. Glucose oxidase (GOx) was chosen as a model bioreceptor to validate the employment of DLC electrodes for bioelectrochemical sensing. In-channel immobilization of glucose oxidase (GOx) at the DLC surface was realized through carbodiimide covalent linkages. Enzyme bound DLC electrode was confirmed with the redox potential at around -79 mV vs NHE in 0.1 M phosphate buffer pH 7.4. Amperometric flow-injection glucose sensing at a potential of -0.45 V vs Ag in the absence of standard redox mediators showed the increase of current response upon increasing the glucose concentration. The sensing mechanism is based on the reduction process of H2O2 liberated from the enzymatic activity. The proposed model for the catalytic H2O2 reduction to H2O on DLC electrodes was attributed to the dissociation of C-O bonds at the DLC surface.